Sulfuric Acid → 3-(3,5-difluorophenyl)-5-methyl-N-(1H-pyrazol-4-ylmethyl)-4,5-dihydro-1,2-oxazole-5-carboxamide

HRID 1522765Notes

Reaction equation

HRID 1522765 reaction equation
Cl.[NH:2]1[CH:6]=[C:5]([CH2:7][NH2:8])[CH:4]=[N:3]1.C(N(CC)C(C)C)(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[F:39][C:40]1[CH:41]=[C:42]([C:47]2[CH2:51][C:50]([CH3:55])([C:52](O)=[O:53])[O:49][N:48]=2)[CH:43]=[C:44]([F:46])[CH:45]=1.OS(O)(=O)=O>ClCCl>[F:46][C:44]1[CH:43]=[C:42]([C:47]2[CH2:51][C:50]([CH3:55])([C:52]([NH:8][CH2:7][C:5]3[CH:6]=[N:2][NH:3][CH:4]=3)=[O:53])[O:49][N:48]=2)[CH:41]=[C:40]([F:39])[CH:45]=1

Participants

8

Reactant 6

HCID 1118Sulfuric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57415873(1H-Pyrazol-4-yl)methanamine hydrochlorideHCID 683869243-(3,5-Difluorophenyl)-5-methyl-4,5-dihydro-1,2-oxazole-5-carboxylic acid

Product 1

HCID 683867093-(3,5-difluorophenyl)-5-methyl-N-(1H-pyrazol-4-ylmethyl)-4,5-dihydro-1,2-oxazole-5-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-(1H-Pyrazol-4-yl)methanamine hydrochloride (609 mg, 4.56 mmol), N,N-diisopropylethylamine (1.61 g, 12.44 mmol), HOBt (506 mg, 4.15 mmol) and EDCI (1.59 g, 8.29 mmol) were added to a solution of 3-(3,5-difluorophenyl)-5-methyl-4,5-dihydro-1,2-oxazole-5-carboxylic acid (1.00 g, 4.15 mmol) in dichloromethane (30 ml), and the mixture was stirred at RT for 16 h. H2SO4 (0.5M, 10 ml) was then added, and the mixture was diluted with CH2Cl2 (20 ml). The aqueous phase was extracted with CH2Cl2 (2×20 ml), the combined organic phases were washed with saturated NaHCO3 solution (30 ml) and dried over Na2SO4, and the solvent was removed. This gave 1.2 g of 3-(3,5-difluorophenyl)-5-methyl-N-(1H-pyrazol-4-ylmethyl)-4,5-dihydro-1,2-oxazole-5-carboxamide which was used without further purification.

Workup

  1. extractionThe aqueous phase was extracted with CH2Cl2 (2×20 ml)
  2. washthe combined organic phases were washed with saturated NaHCO3 solution (30 ml)
  3. dry with materialdried over Na2SO4
  4. customthe solvent was removed
  5. customThis gave 1.2 g of 3-(3,5-difluorophenyl)-5-methyl-N-(1H-pyrazol-4-ylmethyl)-4,5-dihydro-1,2-oxazole-5-carboxamide which was used without further purification

Sources & evidence

ORD record
ord-3c291fd07bd9452cb2ceca067255dbbc
Source dataset
uspto-grants-2015_07
Patent number
US09078442B2

Reaction notes

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